Characteristics of Bachaur bull semen.

The Bachaur is a mediumized draft purpose breed which has been recognized by ICAR-National Bureau of Animal Genetic Resources (NBAGR) Karnal, India, and presently is on the verge of extinction. Since there are no data regarding the seminal parameters of this breed, this work was performed to evaluate seminal parameters of freshly ejaculated semen. A total of three healthy breeding Bachaur bulls aged 2.5-5 years were selected for the study which were maintained under identical managemental conditions. Semen parameters of these bulls were studied across 10 ejaculates. The average scrotal circumference and testicular weight of the three bulls were 27.78 ± 1.2 cm and 400.67 ± 26.6 g, respectively. The average overall volume (mL), pH, concentration (million/mL), liveability (%), abnormality (%), HOST (%) and acrosome integrity (%) were 2.20 ± 0.19, 6.86 ± 0.06, 1245.60 ± 23.49, 85.09 ± 0.91, 4.13 ± 0.06, 81.16 ± 1.18 and 83.54 ± 1.32, respectively. The average overall mass motility of three Bachaur bulls was 3.57 ± 0.06 in 0-5 scale and individual motility averaged 84.78 ± 1.70 per cent. The volume of ejaculates in Bachaur bull seemed to be lower as compared to other exotic and Indian breeds. However, the semen parameters with regard to mass motility, liveability, abnormalities, hypo-osmotic swelling test (HOST) and acrosomal integrity seemed similar to other exotic and Indian breeds.

Switching to coformulated rilpivirine (RPV), emtricitabine (FTC) and tenofovir alafenamide from either RPV, FTC and tenofovir disoproxil fumarate (TDF) or efavirenz, FTC and TDF: 96-week results from two randomized clinical trials.

OBJECTIVES: The single-tablet regimen rilpivirine, emtricitabine and tenofovir alafenamide (RPV/FTC/TAF) for treatment of HIV-1-infected adults was approved based on bioequivalence. We assessed the clinical efficacy, safety and tolerability of switching to RPV/FTC/TAF from either RPV/FTC/tenofovir disoproxil fumarate (TDF) or efavirenz (EFV)/FTC/TDF. METHODS: We conducted two distinct randomized, double-blind, active-controlled, noninferiority trials in participants taking RPV/FTC/TDF (Study 1216) and EFV/FTC/TDF (Study 1160). Each study randomized virologically suppressed (HIV-1 RNA < 50 copies/mL) adults (1:1) to switch to RPV/FTC/TAF or continue their current regimen for 96 weeks. We evaluated efficacy as the proportion with HIV-1 RNA < 50 copies/mL using the Food and Drug Administration snapshot algorithm and prespecified bone and renal endpoints at week 96. RESULTS: We randomized and treated 630 participants in Study 1216 (RPV/FTC/TAF, n = 316; RPV/FTC/TDF, n = 314) and 875 in Study 1160 (RPV/FTC/TAF, n = 438; EFV/FTC/TDF, n = 437). In both studies, the efficacy of switching to RPV/FTC/TAF was noninferior to that of continuing baseline therapy at week 96, with respective percentages of patients with HIV RNA < 50 copies/mL being 89.2% versus 88.5% in Study 1216 [difference 0.7%; 95% confidence interval (CI) -4.3 to +5.8%] and 85.2% versus 85.1% in Study 1160 (difference 0%; 95% CI -4.8 to +4.8%). No participant on RPV/FTC/TAF developed treatment-emergent resistance versus two on EFV/FTC/TDF and one on RPV/FTC/TDF. Compared with continuing baseline therapy, significant improvements in bone mineral density and renal tubular markers were observed in the RPV/FTC/TAF groups (P < 0.001). CONCLUSIONS: Switching to RPV/FTC/TAF from RPV/FTC/TDF or EFV/FTC/TDF was safe and effective and improved bone mineral density and renal biomarkers up to 96 weeks with no cases of treatment-emergent resistance.

In silico analyses of missense mutations in coagulation factor VIII: identification of severity determinants of haemophilia A.

Factor VIII (FVIII) mutations cause haemophilia A (HA), an X-linked recessive coagulation disorder. Over 1000 missense mutations in FVIII are known and they lead to variable clinical phenotypes (severe, moderate and mild). The exact molecular basis of this phenotypic heterogeneity by FVIII missense mutations is elusive to date. In this study, we aimed to identify the severity determinants that cause phenotypic heterogeneity of HA. We compiled and curated a data set of 766 missense mutations from the repertoire of missense mutations in FVIII. We analysed these mutations by computational programs (e.g. Swiss-PdbViewer) and different mutation analysis servers (e.g. SIFT, PROVEAN, CUPSAT, PolyPhen2, MutPred); and various sequence- and structure-based parameters were assessed for any significant distribution bias among different HA phenotypes. Our analyses suggest that 'mutations in evolutionary conserved residues', 'mutations in buried residues', mutation-induced 'steric clash' and 'surface electrostatic potential alteration' act as risk factors towards severe HA. We have developed a grading system for FVIII mutations combining the severity determinants, and the grading pattern correlates with HA phenotype. This study will help to correctly associate the HA phenotype with a mutation and aid early characterization of novel variants.

ERRß signalling through FST and BCAS2 inhibits cellular proliferation in breast cancer cells.

BACKGROUND: The overexpression of oestrogen-related receptor-ß (ERRß) in breast cancer patients is correlated with improved prognosis and longer relapse-free survival, and the level of ERRß mRNA is inversely correlated with the S-phase fraction of cells from breast cancer patients. METHODS: Chromatin immunoprecipitation (ChIP) cloning of ERRß transcriptional targets and gel supershift assays identified breast cancer amplified sequence 2 (BCAS2) and Follistatin (FST) as two important downstream genes that help to regulate tumourigenesis. Confocal microscopy, co-immunoprecipitation (CoIP), western blotting and quantitative real-time PCR confirmed the involvement of ERRß in oestrogen signalling. RESULTS: Overexpressed ERRß induced FST-mediated apoptosis in breast cancer cells, and E-cadherin expression was also enhanced through upregulation of FST. However, this anti-proliferative signalling function was challenged by ERRß-mediated BCAS2 upregulation, which inhibited FST transcription through the downregulation of ß-catenin/TCF4 recruitment to the FST promoter. Interestingly, ERRß-mediated upregulation of BCAS2 downregulated the major G1-S transition marker cyclin D1, despite the predictable oncogenic properties of BCAS2. INTERPRETATION: Our study provides the first evidence that ERRß, which is a coregulator of ERα also acts as a potential tumour-suppressor molecule in breast cancer. Our current report also provides novel insights into the entire cascade of ERRß signalling events, which may lead to BCAS2-mediated blockage of the G1/S transition and inhibition of the epithelial to mesenchymal transition through FST-mediated regulation of E-cadherin. Importantly, matrix metalloprotease 7, which is a classical mediator of metastasis and E-cadherin cleavage, was also restricted as a result of ERRß-mediated FST overexpression.

A protein linkage map of Escherichia coli bacteriophage T7.

Genome sequencing projects are predicting large numbers of novel proteins, whose interactions with other proteins must mediate the function of cellular processes. To analyse these networks, we used the yeast two-hybrid system on a genome-wide scale to identify 25 interactions among the proteins of Escherichia coli bacteriophage T7. Among these is a set of six interactions connecting proteins that function in DNA replication and DNA packaging. Remarkably, two genes, arranged such that one entirely overlaps the other and uses a different reading frame, encode interacting proteins. Several of the interactions reflect intramolecular associations of different domains of the same polypeptide, suggesting that the two-hybrid assay may be useful in the analysis of protein folding. This global approach to protein-protein interactions may be applicable to the analysis of more complex genomes whose sequences are becoming available.

Development of non-exercise based VO2max prediction equation in college-aged participants in India.

AIM: The purpose of this study was to develop a linear regression model to predict treadmill VO2max scores using non-exercise data. METHODS: In this cross sectional study, one hundred twenty college-aged participants (60 male, 60 female, mean age 22.02±2.29 years) voluntarily participated and successfully completed a maximal graded exercise test (GXT) on a motorized treadmill to assess VO2max (mean±SD; 2.05 L·min-¹±1.03 L·min-¹). The maximal treadmill GXT required participants to exercise to volitional fatigue. RESULTS: Relevant non-exercise data included a mean (±SD) perceived functional ability (PFA) score, and physical activity rating (PA-R) score, body surface area (BSA) of 14.6±3.9, 2.97±1..75, 1.66±0.17, respectively. Multiple linear regression generated the following regression equation (R=0.899, R2=0.805, adjusted R2=0.799, SEE=0.426 L·min-¹): VO2max (L/min)=-1.541+1.096 (gender, 1=male, 0=female) +.081 (PFA) +1.084(BSA). Each predictor variable was statistically significant (P<0.05) with beta weights for gender, PFA, BSA, PA-R, and equal to (-0.518), (0.255), (0.228), (0.092), percent body fat (-0.003), respectively. The accuracy of the model was evaluated by conducting a cross-validation analysis (N.=18). CONCLUSION: This study provides a N-EX regression prediction model that yields results and also provide a convenient and efficient tool that estimate VO2max in healthy college-aged participants in India.

The neuronal repressor REST/NRSF is an essential regulator in medulloblastoma cells.

Medulloblastoma is the most malignant pediatric brain tumor. It is believed to originate from the undifferentiated external granule layer cells in the cerebellum, but the mechanism of tumorigenesis remains unknown. Here we studied three types of human medulloblastoma cells that express markers corresponding to different levels of neuronal differentiation. They expressed the neuronal repressor element 1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF; refs. 7-10) at very high levels compared with either neuronal progenitor NTera2 (NT2) cells or fully differentiated human neuron teratocarcinoma (hNT cells). To counter the effect of REST/NRSF, we used a recombinant transcription factor, REST-VP16, constructed by replacing repressor domains of REST/NRSF with the activation domain of viral protein (VP16). Transient expression of REST-VP16 in medulloblastoma cells was able to compete with the endogenous REST/NRSF for DNA binding and stimulate neuronal promoters. High-efficiency expression of REST-VP16 mediated by adenovirus vectors (Ad.REST-VP16) in medulloblastoma cells was able to counter REST/NRSF-mediated repression of neuronal promoters, stimulate expression of endogenous neuronal genes and trigger apoptosis through the activation of caspase cascades. Furthermore, intratumoral injection of Ad.REST-VP16 in established medulloblastoma tumors in nude mice inhibited their growth. Therefore, REST/NRSF may serve as a new target for therapeutic interventions for medulloblastoma through agents such as REST-VP16.

Strand-specific recognition of a synthetic DNA replication fork by the SV40 large tumor antigen.

The mechanism by which DNA helicases unwind DNA was tested; an "unwinding complex" between the SV40 large tumor antigen (T antigen) and a DNA molecule designed to resemble a replication fork was probed. In an adenosine triphosphate (ATP)-dependent reaction, T antigen quantitatively recognized this synthetic replication fork and bound the DNA primarily as a hexamer. The T antigen bound only one of the two strands at the fork, an asymmetric interaction consistent with the 3'----5' directionality of the DNA helicase activity of T antigen. Binding to chemically modified DNA substrates indicated that the DNA helicase recognized the DNA primarily through the sugar-phosphate backbone. Ethylation of six top strand phosphates at the junction of single-stranded and double-stranded DNA inhibited the DNA helicase activity of T antigen. Neither a 3' single-stranded end on the DNA substrate nor ATP hydrolysis was required for T antigen to bind the replication fork. These data suggest that T antigen can directly bind the replication fork through recognition of a fork-specific structure.

Multiscale modeling catalytic decomposition of hydrocarbons during carbon nanotube growth.

A molecular dynamics simulator coupled to a quantum semiempirical Hamiltonian model was applied to multiscale modeling of the catalytic decomposition of hydrocarbons during carbon nanotube (CNT) and carbon nanofiber (CNF) growth. It was found that catalytic decomposition of acetylene is accompanied by a large energy release and its rate weakly depends on temperature in the range from 20 to 700 degrees C. In contrast, the methane decomposition rate substantially decreases as the iron temperature drops. A comparative analysis of acetylene decomposition on a clean surface and on an oxidized Fe(100) surface showed that the presence of oxygen reduces the decomposition rate by an order of magnitude, but has very little influence on the amount of heat released by the reaction. We also found that oxygen absorbed on the surface of catalyst does not easily diffuse into the catalyst or desorb from the surface. This implies that the surface of the catalyst is quickly covered by oxygen during CNT/CNF growth even at low oxygen flow rates.

Biomechanical Analysis of CT Scan-based Hip Prosthesis With an Optimal Hip Ball by Using Finite Element Analysis.

Bone loss around the femoral stems during the insertion of a standard prosthesis is a major problem in hip arthroplasty. Moreover, long periods of use of the standard metallic prosthesis often lead to revision surgery because of disuse osteoporosis (stress shielding). The main factor behind this problem is the material-stiffness mismatch of the bone and implant, with the latter consisting of metals such as stainless steel, Co-Cr-Mo alloy, or Ti6Al4V alloy. Our study aimed to decrease the factor of geometric mismatch by designing and making customized hip prostheses from computed tomography scan data and finite element analysis. Therefore, the inner medullar cavity of the femur would match exactly with the prosthesis. Our results showed that the desired stress-strain values were close to the physiological level. We observed that the maximum Von Mises stresses for the bone and implant were 41.8 MPa and 197 MPa, respectively. An optimization analysis of the taper angle of the prosthesis hip ball for fixation with the stem has also been performed, in which the angle was found to be approximately 2 deg. The taper angle plays an important role in load transfer and safe levels of stress-strain using various ball materials.

Lipid composition and salt concentration as regulatory factors of the anion selectivity of VDAC studied by coarse-grained molecular dynamics simulations.

The voltage-dependent anion channel (VDAC) is a mitochondrial outer membrane protein whose fundamental function is to facilitate and regulate the flow of metabolites between the cytosol and the mitochondrial intermembrane space. Using coarse-grained molecular dynamics simulations, we investigated the dependence of VDAC selectivity towards small inorganic anions on two factors: the ionic strength and the lipid composition. In agreement with experimental data we found that VDAC becomes less anion selective with increasing salt concentration due to the screening of a few basic residues that point into the pore lumen. The molecular dynamics simulations provide insight into the regulation mechanism of VDAC selectivity by the composition in the lipid membrane and suggest that the ion distribution is differently modulated by POPE compared to the POPC bilayer. This occurs through the more persistent interactions of acidic residues located at both rims of the ß-barrel with head groups of POPE which in turn impact the electrostatic potential and thereby the selectivity of the pore. This mechanism occurs not only in POPE single component membranes but also in a mixed POPE/POPC bilayer by an enrichment of POPE over POPC lipids on the surface of VDAC. Thus we show here that computationally-inexpensive coarse-grained simulations are able to capture, in a semi-quantitative way, essential features of VDAC anion selectivity and could pave the way toward a molecular level understanding of metabolite transport in natural membranes.

Efficacy of Heatsynch protocol for induction of estrus, synchronization of ovulation and timed artificial insemination in yaks (Poephagus grunniens L.).

The objective of this study was to test the efficacy of induction of estrus, synchronization of ovulation and timed artificial insemination in anestrous yaks using the Heatsynch protocol. In Experiment 1, 10 anestrous yaks were administered an analogue of gonadotropin releasing hormone (GnRH) followed by prostaglandin (PG)F2alpha 7 days later and then estradiol cyponate (ECP) 24 h after that. Ovulation was detected by rectal palpation at 2h intervals beginning at the initial signs of estrus. Blood samples were collected at 2h intervals beginning at the time of ECP injection up to 2h after the occurrence of ovulation for the determination of LH and progesterone. All the animals responded to the Heatsynch protocol with expression of estrus and synchronization of ovulation. The mean time interval from the ECP injection to ovulation was 59.4+/-2.62 h (range 50-72 h). The interval from the LH peak to ovulation was 30.2+/-2.3 h. The high degree of synchrony in ovulation could be attributed to the synchrony in the timing of LH peaks. In Experiment 2, 10 anestrous yaks were treated with the Heatsynch protocol (as in Experiment 1) and TAI was performed at 48 and 60 h after the ECP treatment. Concurrently, 16 cycling yaks were inseminated approximately 12 h after detection of spontaneous estrus. Pregnancy rates were similar in both groups, 40% for TAI and 43.75% for yaks inseminated following spontaneous estrus (p>0.05). From this study, two conclusions can be drawn. First, the Heatsynch protocol can be successfully used to induce and synchronize estrus in anestrous yaks and, second, ovulation following the Heatsynch protocol is synchronized adequately to permit the use of fixed time AI in this species.

Estimation of radon exhalation rate, natural radioactivity and radiation doses in fly ash samples from Durgapur thermal power plant, West Bengal, India.

Coal and its by products often contain significant amounts of radionuclides, including uranium which is the ultimate source of the radioactive gas radon. Burning of coal and the subsequent emission to the atmosphere cause the re-distribution of toxic trace elements in the environment. Due to considerable economic and environmental importance and diverse uses, the collected fly ash has become a subject of worldwide interest in recent years. In the present study, radon exhalation rate and the activity concentration of (238)U, (232)Th and (40)K radionuclides in fly ash samples from Durgapur thermal power plant (WB) have been measured by "Sealed Can technique" using LR-115 type II detectors and a low level NaI (Tl) based gamma ray spectrometer, respectively. Radon exhalation rate varied from 360.0 to 470.0 mBq m(-2)h(-1) with an average value of 406.8 mBq m(-2)h(-1). Activity concentrations of (238)U ranged from 84.8 to 126.4 Bq kg(-1) with an average value of 99.3Bqkg(-1), (232)Th ranged from 98.1 to 140.5 Bq kg(-1) with an average value of 112.9 Bq kg(-1) and (40)K ranged from 267.1 to 364.9 Bq kg(-1) with an average value of 308.9 Bq kg(-1). Radium equivalent activity obtained from activity concentrations is found to vary from 256.5 to 352.8 Bq kg(-1) with an average value of 282.5 Bq kg(-1). Absorbed gamma dose rates due to the presence of (238)U, (232)Th and (40)K in fly ash samples vary in the range 115.3-158.5 nGy h(-1) with an average value of 126.4 nGy h(-1). While the external annual effective dose rate varies from 0.14 to 0.19 mSv y(-1) with an average value of 0.15 mSv y(-1), effective dose equivalent estimated from exhalation rate varies from 42.5 to 55.2 microSv y(-1) with an average value of 47.8 microSv y(-1). Values of external hazard index H(ex) for the fly ash samples studied in this work range from 0.69 to 0.96 with a mean value of 0.77.

An investigation of radon exhalation rate and estimation of radiation doses in coal and fly ash samples.

Coal is a technologically important material used for power generation. Its cinder (fly ash) is used in the manufacturing of bricks, sheets, cement, land filling etc. Coal and its by-products often contain significant amounts of radionuclides, including uranium which is the ultimate source of the radioactive gas radon. Burning of coal and the subsequent atmospheric emission cause the redistribution of toxic radioactive trace elements in the environment. In the present study, radon exhalation rates in coal and fly ash samples from the thermal power plants at Kolaghat (W.B.) and Kasimpur (U.P.) have been measured using sealed Can technique having LR-115 type II detectors. The activity concentrations of 238U, 232Th, and 40K in the samples of Kolaghat power station are also measured. It is observed that the radon exhalation rate from fly ash samples from Kolaghat is higher than from coal samples and activity concentration of radionuclides in fly ash is enhanced after the combustion of coal. Fly ash samples from Kasimpur show no appreciable change in radon exhalation. Radiation doses from the fly ash samples have been estimated from radon exhalation rate and radionuclide concentrations.

Noncontrast Head CT in Children: National Variation in Radiation Dose Indices in the United States.

BACKGROUND AND PURPOSE: Radiologists should manage the radiation dose for pediatric patients to maintain reasonable diagnostic confidence. We assessed the variation in estimated radiation dose indices for pediatric noncontrast head CT in the United States. MATERIALS AND METHODS: Radiation dose indices for single-phase noncontrast head CT examinations in patients 18 years of age and younger were retrospectively reviewed between July 2011 and June 2016 using the American College of Radiology CT Dose Index Registry. We used the reported volume CT dose index stratified by patient demographics and imaging facility characteristics. RESULTS: The registry included 295,296 single-phase pediatric noncontrast head CT studies from 1571 facilities (56% in male patients and 53% in children older than 10 years of age). The median volume CT dose index was 33 mGy (interquartile range = 22-47 mGy). The volume CT dose index increased as age increased. The volume CT dose index was lower in children's hospitals (median, 26 mGy) versus academic hospitals (median, 32 mGy) and community hospitals (median, 40 mGy). There was a lower volume CT dose index in level I and II trauma centers (median, 27 and 32 mGy, respectively) versus nontrauma centers (median, 40 mGy) and facilities in metropolitan locations (median, 30 mGy) versus those in suburban and rural locations (median, 41 mGy). CONCLUSIONS: Considerable variation in the radiation dose index for pediatric head CT exists. Median dose indices and practice variations at pediatric facilities were both lower compared with other practice settings. Decreasing dose variability through proper management of CT parameters in pediatric populations using benchmarks generated by data from registries can potentially decrease population exposure to ionizing radiation.

Emergence of dalbavancin non-susceptible, vancomycin-intermediate Staphylococcus aureus (VISA) after treatment of MRSA central line-associated bloodstream infection with a dalbavancin- and vancomycin-containing regimen.

OBJECTIVES: Dalbavancin is a long-acting lipoglycopeptide with activity against gram-positives, including methicillin-resistant Staphylococcus aureus (MRSA). The potential for lipoglycopeptides, with half-lives greater than 1 week, to select for resistance is unknown. Here we explore a case of MRSA central line-associated bloodstream infection in which dalbavancin and vancomycin non-susceptibility emerged in a urine isolate collected after the patient was treated with vancomycin and dalbavancin sequentially. METHODS: Isolates from blood and urine underwent susceptibility testing, and whole genome sequencing (WGS). The blood isolate was subjected to successive passage in vitro in the presence of escalating dalbavancin concentrations and the emergent isolate was subjected to repeat susceptibility testing and WGS. RESULTS: The blood isolate was fully susceptible to vancomycin; however, MICs of the urine isolate to dalbavancin, vancomycin, telavancin, and daptomycin were at least fourfold higher than the blood-derived strain. Both strains were indistinguishable by spa and variable number tandem repeat (VNTR) typing, and WGS revealed only seven variants, indicating clonality. Four variants affected genes, including a 3bp in-frame deletion in yvqF, a gene which has been implicated in glycopeptide resistance. Vancomycin and dalbavancin non-susceptibility emerged in the blood isolate after successive passage in vitro in the presence of dalbavancin, and WGS identified a single non-synonymous variant in yvqF. CONCLUSIONS: This is the first case in which VISA has emerged in the context of a dalbavancin-containing regimen. The selection for cross-resistance to vancomycin in vitro by dalbavancin exposure alone is troubling. Clinicians should be aware of the possibility for emergence of dalbavancin non-susceptibility and glycopeptide cross-resistance arising following therapy.

Cell-cycle-specific and serum-dependent expression of gamma-actin mRNA in Swiss mouse 3T3 cells.

We isolated cDNA clones that represent genes whose expression is enhanced when resting Swiss mouse 3T3 cells are stimulated to proliferate with serum. Two clones (designated pME1 and pMR6) were analyzed further. A partial sequence analysis of the pME1 insert DNA indicated that it contained a 104-base-pair stretch with extensive homology to the 3' untranslated region of gamma actin. Similar analysis of the insert DNA from the pMR6 clone indicated that it did not correspond to any previously reported gene sequence. We used the pME1 clone as a probe to determine the level of gamma actin-specific transcript in 3T3 cells under a variety of conditions. The level of gamma actin-specific mRNA began to increase in resting cells upon serum stimulation and reached a peak at 6 h. Thereafter its level declined, and by 24 h it was hardly detectable. In contrast, pMR6-specific transcript was detectable in resting cells but remained elevated even at 24 h poststimulation. The level of gamma-actin mRNA was elevated in resting cells by 12-O-tetradecanoylphorbol-13-acetate, calcium ionophore A23187, and bombesin and to a lesser extent by cholera toxin, fibroblast-derived growth factor, and dibutyryl cyclic AMP. However, insulin, vasopressin, or epidermal growth factor failed to enhance gamma-actin mRNA levels in resting cells. Inhibitors of transcription diminished the induction of gamma-actin mRNA. Gamma-actin gene was superinduced in serum-stimulated cells by cycloheximide, an inhibitor of translation. Analysis of proteins from serum-stimulated cells by two-dimensional gel electrophoresis indicated that enhanced transcription of gamma-actin mRNA resulted in a concomitant increase in the corresponding actin protein. The possible role of gamma actin, a component of the cytoskeleton, in the regulation of cell growth is discussed.

Bacteroides are associated with GALT iNKT cell function and reduction of microbial translocation in HIV-1 infection.

Invariant natural killer T (iNKT) cells are innate-like T cells that respond to lipid antigens presented by CD1d. These immunoregulatory cells have the capacity for rapid cytokine release after antigen recognition and are essential for the activation of multiple arms of the immune response. HIV-1 infection is associated with iNKT cell depletion in the peripheral blood; however, their role in the gastrointestinal-associated lymphoid tissue (GALT) is less well studied. Our results show that iNKT cells are found at a higher frequency in GALT compared with blood, particularly in HIV-1 elite controllers. The capacity of iNKT cells to produce interleukin-4 (IL-4) and IL-10 in the GALT was associated with less immune activation and lower markers of microbial translocation, whereas regulatory T cell frequency showed positive associations with immune activation. We hypothesized that the composition of the microbiota would influence iNKT cell frequency and function. We found positive associations between the abundance of several Bacteroides species and iNKT cell frequency and their capacity to produce IL-4 in the GALT but not in the blood. Overall, our results are consistent with the hypothesis that GALT iNKT cells, influenced by certain bacterial species, may have a key role in regulating immune activation in HIV-1 infection.

Impaired dimensional selection but intact use of reward feedback during visual discrimination learning in Parkinson's disease.

It has been suggested that Parkinson's disease (PD) impairs the ability to learn on the basis of reward or reinforcing feedback i.e., by trial-and-error. In many learning tasks, particular 'dimensions' of stimulus information are relevant whilst others are irrelevant; therefore, efficient performance depends on identifying the dimensions of these 'compound' stimuli and selecting the relevant dimension for further processing. We investigated the ability of patients with PD, as well as patients with Huntington's disease and patients with frontal or temporal lobe lesions, to learn visual discriminations which required either a number of associations to be learned concurrently (the 'eight-pair' task) or the selection of information from compound stimuli (the 'five-dimension' task), both tasks being learned by trial-and-error. None of the basal ganglia disorder patient groups was impaired on the eight-pair task, militating against a crucial role for these brain structures in trial-and-error learning per se. Patients with mild, medicated PD, but not unmedicated PD patients, were impaired at identifying all five feature dimensions in the five-dimension task, implying dopaminergic 'overdosing' of the ability to analyse compound stimuli in terms of their component dimensions. Temporal lobe lesion patients performed similarly, suggesting that the temporal lobe may be the site of the medication overdose effect. Patients with severe, medicated PD were impaired at compound discrimination learning on the five-dimension task in the absence of an underlying impairment in identifying component stimulus dimensions; this pattern resembled that seen in Huntington's disease and frontal lobe lesion patients, implying that fronto-striatal circuitry is involved in the formation of rules based upon selected stimulus dimensions.

Limitation of glucose oxidase method of glucose estimation in jaundiced neonates.

The most widely used method for estimation of plasma glucose is that adopted by Trinder's using glucose oxidase-peroxidase (GOD-POD) system. This method gives much lower blood glucose values with blood samples of neonatal jaundice (plasma bilirubin level > 10 mg/dL) of age 10 +/- 5 daysthan with samples of neonates of the same age group without jaundice or older children suffering from other diseases like acute respiratory distress, septicemia.